MELANOMA CRITICAL DEBATES - PART 1 ppt

Consultant Cancer PhysicianRoyal Marsden Hospital London UK Blackwell Science... List of contributorseditors Julia Newton BishopMB ChB MD FRCP, Consultant Dermatologist, Honorary Reader

CRITICAL DEBATES

Consultant Cancer Physician

Royal Marsden Hospital

London

UK

Blackwell

Science

Library of Congress Cataloging-in-Publication Data

Melanoma: Critical Debates /edited by J A Newton Bishop, M Gore.

A catalogue record for this title is available from the British Library

Set in 10/13 1 /2Sabon by SNP Best-set Typesetter Ltd, Hong Kong

Printed and bound in Great Britain by MPG Books Ltd, Bodmin, Cornwall

For further information on Blackwell Publishing, visit our website:

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List of contributors, vii

Introduction, x

Part 1: Aetiology

1 m berwick: Patterns of sun exposure which are causal

for melanoma, 3

2 p autier: Are sunbeds dangerous? 16

3 a.r young: Do sunscreens cause cancer or protect from a risk ofmelanoma? 30

4 j rees: Why are redheads so susceptible to melanoma? 49

5 j.a newton bishop: The management of patients with atypicalnaevi, 61

6 r.f kefford: Guidelines for the management of those at high riskfor developing cutaneous melanoma, 70

7 n kirkham: Borderline melanocytic lesions, 78

Part 2: Diagnosis, Screening and Prevention

8 w bergman: How can we improve the early diagnosis of melanoma?89

9 m elwood: What are the prospects for population screening formelanoma? 106

Part 3: Management

10 m.j timmons: Excision of primary cutaneous melanoma, 123

v

Contents

11 r.a popescu, p.m patel and j spencer: Imaging and

investigation of melanoma patients, 133

12 d ross and m.i ross: The management of regional lymph noderelapse in melanoma, 150

13 j.a newton bishop and r happle: Congenital melanocyticnaevi, 168

14 j.c newby and t eisen: The role of chemotherapy, 178

15 a.m.m eggermont and u keilholz: What is the role of biological response modifiers in the treatment of melanoma? 195

16 p hersey: Will vaccines really work for melanoma? 212

17 f.j lejeune and d liénard: Who should we consider for isolated limb perfusion? 230

18 s.s legha: Novel strategies for the treatment of melanoma, 238

19 j evans: Who should follow up melanoma patients and for how long?248

20 a.g goodman: What is the role for radiotherapy in melanoma? 257

21 s.r.d johnston: What should we tell patients about hormonesafter having melanoma? 269

Index, 281

List of contributors

editors

Julia Newton BishopMB ChB MD FRCP, Consultant Dermatologist, Honorary Reader in Dermatological Oncology, ICRF Senior Clinical Scientist, ICRF Cancer Medicine Research Unit, St James’s University Hospital, Beckett Street, Leeds

LS9 7TF, UK

Martin GoreMB BS PhD FRCP, Consultant Cancer Physician, Royal Marsden

Hospital, Fulham Road, London SW3 6JJ, UK

contributors

Phillipe AutierMD MPH, Deputy Director, Division of Epidemiology and

Biostatitics, European Institute of Oncology, 1135 Ripamonti, Milan, Italy

Wilma BergmanMD PhD, Department of Dermatology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands

Marianne BerwickPhD, Division of Epidemiology and Biostatistics, Box 44,

Memorial Sloan Kettering Hospital, 1275 York Ave, New York, NY10021, USA

Alexander EggermontMD PhD, Surgical Oncologist, Department of Surgical Oncology, Daniel Den Hoed Cancer Centre, 301 Groene Hilledijk, 3075 EA,

Rotterdam, The Netherlands

Tim EisenPhD MRCP, Senior Lecturer and Consultant Medical Oncologist,

Department of Medicine, Institute of Cancer Research, The Royal Marsden Hospital, Downs Road, Sutton, Surrey SM2 5PT, UK

Mark Elwood MD DSc FFPHM, Director, National Cancer Control Initiative,

1 Rathdowne Street, Carlton (Melbourne), Victoria, 3053, Australia

Judy Evans MA FRCSEd (PLAST) FRCS, Nuffield Hospital, Derriford Road,

Plymouth, Devon PL6 8BG, UK

Andrew GoodmanMRCP FRCR, Lead Clinician, Department of Oncology, Devon and Exeter Hospital, Barrack Road, Exeter, EX2 5DW, UK

vii

Rudolf Happle MD, Professor of Dermatology, Department of Dermatology and Allergology, Phillipp University of Marburg, Deutschhausstrabe 9, 35033 Marburg, Germany

Peter HerseyFRACP D.Phil, Room 443, David Maddison Building, Cnr King & Watt Street, Newcastle NSW 2300, Australia

Stephen JohnstonMA MRCP PhD, Consultant Medical Oncologist, Department of Medicine, Royal Marsden Hospital, Fulham Road, London SW3 6JJ, UK

Richard Kefford MB BS (Syd) PhD FRACP, Professor of Medicine and Director, Westmead Institute for Cancer Research, University of Sydney at Westmead Millenium Institute, Westmead, NSW 2145, Australia

Ulrich KeilholzMD PhD, University Hospital Benjamin Franklin, Free University Berlin, Hindenburhdamm 30, D-12200 Berlin, Germany

Nigel KirkhamMD FRCPath, Consultant Pathologist, Department of

Histopathology, Royal Sussex County Hospital, Brighton BN2 5BE, UK

Sewa LeghaMD FACP, 8501 Hawaii Lane, Houston, Texas, 77040, USA

Ferdy Lejeune MD PhD, Professor of Oncology and Director of Centre

Pluridisciplinaire d’Oncologie, Centre Hospitalier Universitaire Vaudois, Rue du Bugnon 46, CH-1011 Lausanne, Switzerland

Danielle Liénard MD, Medecin Associe and Consultant, Centre Pluridisciplinaire d’Oncologie and Principal Clinical Investigator, Ludwig Institute for Cancer Research, Centre Hospitalier Universitaire Vaudois, Rue du Bugnon 46, CH-1011 Lausanne, Switzerland

Jacqueline NewbyMA MRCP MD, Senior Registrar in Medical Oncology, 18 Barncroft Way, St Albans, Hertfordshire AL1 5QZ, UK

Poulam Patel MD MRCP, Consultant Medical Oncologist and ICRF

Clinical Scientist, ICRF Cancer Medicine Research Unit, St James’s University Hospital, Beckett Street, Leeds LS9 7TF

Razvan PopescuMD MRCP, Department of Oncology, Centre Hospitalier

Universitaire Vaudois, Rue du Bugnon 46, BH06, CH-1011 Lausanne, Switzerland

Jonathan ReesFRCP FMedSci, Department of Dermatology, University of

Edinburgh, Royal Infirmary Lauriston Building, Lauriston Place, Edinburgh

Merrick Ross MD FACS, Professor of Surgery, Chief of Melanoma and Sarcoma Division, Department of Surgical Oncology, The MD Anderson Cancer Center,

1515 Holcombe Boulevard, Houston, Texas, USA

John Spencer MD FRCR, Consultant Radiologist, Department of Radiology,

St James’s University Hospital, Beckett Street, Leeds LS9 7TF, UK

Michael TimmonsMA MChir FRCS, Consultant Plastic Surgeon, Department of Plastic Surgery, Bradford Royal Infirmary, Duckworth Lane, Bradford BD9 6RJ, UK

Antony YoungPhD, Department of Environmental Dermatology, St John’s Institute

of Dermatology, Guy’s, King’s and St Thomas’ School of Medicine, King’s College London, University of London, St Thomas’ Hospital, London SE1 7EH, UK

LIST OF CONTRIBUTORS ix

x

The treatment of melanoma is indeed a debate and this book is intended to address the major areas of controversy in a practical way It is written with thehealth care professional in mind who is part of the multidisciplinary teamwhich manages the disease from screening to palliative care

The incidence of melanoma has increased dramatically in North America,Europe and Australasia this century [1] which is attributed to changed pat-terns of behaviour of white-skinned peoples in the sun [2–4] The first chapter

by Marianne Berwick addresses the issues which remain to be resolved, cerning the critical patterns of sun exposure and the age at which it occurs Artificial ultraviolet light (UV) exposure allows individuals in colder climates

con-to expose their skin con-to UV doses hithercon-to unprecedented, which has tially grave effects on the incidence of melanoma in these populations Theissue of sunbeds is addressed by Philippe Autier in Chapter 2 Protection fromthe carcinogenic effects of UV is clearly important There has been concernhowever, that although sunscreens demonstrably reduce the ill-effects of UVlight [5,6], that the general public has become too reliant on sunscreens Therehas even been the suggestion that over-reliance on sunscreens may encouragechildren to stay out in the sun for longer which might even increase their susceptibility to melanoma [7–9] Antony Young discusses these issues inChapter 3

poten-The white population is the primary group at risk of developing melanomaand there is clear variation in susceptibility to skin cancer within this popula-tion Epidemiological studies established the increased susceptibility of sunsusceptible phenotypes such as red hair to skin cancer [10] and understanding

of the molecular basis of this has been developed by Jonathan Rees who scribes this progress in Chapter 4 The presence of multiple melanocytic naevi,

de-or moles, is however, a mde-ore potent risk factde-or fde-or melanoma [11,12] Thosewho manifest this so-called atypical naevus phenotype (or dysplastic naevusphenotype) are a challenge, particularly to dermatologists and primary healthcare physicians, not least because the phenotype is common, occurring in atleast 2% of the population [13] (chapter 5)

INTRODUCTION xi

It is postulated that the sun susceptible phenotype and the atypical molesyndrome are due to low penetrance melanoma susceptibility genes Muchmore rarely, families can carry germ-line high-penetrance susceptibility genesand have a strong family history of melanoma These families were initially described in the 19th century by Norris [14] but first explored in the 1980s[15,16] A significant proportion of the largest of these families, are nowshown to be caused by germline mutations in the CDKN2A gene which codesfor the protein p16 In Chapter 6, Richard Kefford discusses familial predis-position to melanoma in general terms and the specifics of genetic testing.One of the great challenges is the early detection of melanoma, particularlyperhaps in areas of relatively low incidence, such as Europe and some parts ofthe USA In the UK primary health care teams see very few early tumours intheir working lifetime and the population perceives the risk of melanoma to

be low In the skin cancer screening clinic, often named the pigmented lesion

clinic, the challenge is to diagnose melanomas at the in situ stage when cure is

the result of excision, in a cost-effective way This challenge is considerable, asthe appearances are subtle and difficult to distinguish from the common atyp-ical naevus Wilma Bergman discusses approaches to this problem in Chapter

8 Management problems do not end at excision, there are difficulties in thehistopathological diagnosis of early melanocytic lesions which are discussed

by Nigel Kirkham in Chapter 7 The pigmented lesion clinics represent tunist screening and allow expertise to be concentrated in one place In areas

oppor-of high incidence oppor-of melanoma, it is possible that active screening might be acost-effective exercise In Chapter 9, Mark Elwood discusses different ap-proaches to screening at different latitudes and therefore within differentbackgrounds of melanoma incidence

Patients with congenital naevi, particularly the giant pigmented type, are

at increased risk of melanoma [17,18] but there is uncertainty about the magnitude of that risk In clinical practice a balance is needed between the potential value of surgery for these naevi and any potential cosmeticdeficit This issue is discussed by Julia Newton Bishop and Rudolf Happle inChapter 13

The treatment of melanoma is still essentially surgical but there remainsconsiderable controversy about the optimal margins of excision of the pri-mary tumour There are randomized clinical trial data to support a 1 cm margin for tumours less than 2 mm in Breslow thickness [19] and some dataconcerning the safety of margins for thicker tumours [20] There are also different approaches to excision margins for tumours thinner than 1 mm withsome clinicians choosing to remove these with a 0.5 cm margin and others con-sidering that this is only appropriate when the lesion is in radial growth phase[21], as the likelihood of recurrence is thought to be low in such circumstances[22,23] There is a particular lack of trial data on what constitutes safe

margins of excision for lentigo maligna and nail bed/subungual melanomas.These issues are discussed by Michael Timmons in Chapter 10.

In patients at risk of relapse there is no evidence that intensive staging procedures, or follow up involving regular imaging in order to diagnose earlyrelapse, alters survival In Chapter 11, John Spencer, Razvan Popescu andPoulam Patel discuss the need to balance the radiation dosage of computerizedtomography, the relatively high false positivity of scans and the resulting anxiety that can be caused They also discuss the value of different stagingstrategies The absence of effective systemic therapy for melanoma means thatmost guidelines recommend follow up should be predominantly clinical [24].However, there is some controversy as to whether fit patients who might contemplate aggressive therapy with IL-2 based treatments benefit from earlyintervention and thus a more aggressive follow-up policy The organization ofclinical follow up is discussed by Judy Evans in Chapter 19

The surgical treatment of lymph node relapse remains controversial eral trials have failed to show any survival benefit of elective lymph node exci-sion [25,26] Sentinel node biopsy is a modification of the approach whichuses lymphoscintigraphy and dye to localize the principal draining lymphnodes [27] The technique is undoubtedly of value as a staging procedure but

Sev-it remains to be seen whether Sev-it impacts on survival David Ross and MerrickRoss discuss the issues that are evolving around this technology in Chapter 12.The treatment of patients with advanced melanoma is as yet ineffective interms of impacting survival, although chemotherapy has a valuable palliativerole and this is discussed by Tim Eisen and Jaqueline Newby in Chapter 14.There is hope that the biological response modifiers, immunotherapy andsome of the newer agents with novel mechanisms of action may offer morehope in both the adjuvant setting and for the treatment of metastatic disease.Alexander Eggermont, Ulrich Keilholz and Sewa Legha discuss these topics inChapters 15 and 18 It is recognised that patients and the health care team are somewhat emotionally invested in vaccines for cancer therapy and this important area of research is reviewed by Peter Hersey in Chapter 16

Sometimes disease recurs in a limb and in this situation surgery or CO2laser therapy is the treatment of choice However, isolated limb perfusion is ofgreat value when control is being lost and its role is outlined by Ferdy Lejeuneand Danielle Liénard in Chapter 17 The use of radiotherapy in palliation and its limitations are described by Andrew Goodman in Chapter 20 and finally Stephen Johnston discusses the possible role of female hormones andpregnancy in melanoma in the last chapter of the book

Melanoma is a disease that engenders much negativity in many tic circles However, it is a cancer which requires great care and attention if patients are to be managed optimally Expertise is required at every stage of thepatient’s journey from early diagnosis to the palliation metastatic disease It is

a tumour that is increasing in frequency, but so is our knowledge of its biologyand it is only a matter of time before we will make a significant impact on thesurvival of patients.

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INTRODUCTION xiii

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Julia Newton Bishop Martin Gore

Part 1: Aetiology

Melanoma: Critical Debates

Edited by Julia A Newton Bishop, Martin Gore Copyright © 2002 Blackwell Science Ltd